Treatment Strategy for Atrial Fibrillation

Transcription

1 Rhythm or rate control in persistent atrial fibrillation Peter G. Guerra, Denis Roy Department of Medicine and Research Center, Montreal Heart Institute, Montreal, Quebec, Canada Selecting appropriate treatment strategies for patients with persistent atrial fibrillation has often proved to be a quandary. Foregoing any debate on anticoagulant therapy, the remaining issue is whether the ultimate goal should be achieving and maintaining sinus rhythm or simply controlling the ventricular response during ongoing atrial fibrillation. Since atrial fibrillation affects 5% of the population over the age of 60 and increases with advanced age, it is a question of utmost clinical relevance [1]. Atrial fibrillation may be classified as paroxysmal, persistent, or chronic. Paroxysmal atrial fibrillation can be defined as AF which is self-limited, converting spontaneously to sinus rhythm; persistent AF is defined as necessitating an electrical or chemical cardioversion; whereas permanent or chronic AF does not respond to these maneuvers. For the purposes of this article, the focus will be on the treatment of persistent atrial fibrillation, as it is the subset which most often will require interventions to restore and maintain sinus rhythm. Persistent atrial fibrillation can be asymptomatic, but it is often associated with symptoms of palpitations, dyspnea and chest pains. Angina and congestive heart failure can be precipitated or aggravated by atrial fibrillation. Rapid ventricular rates during atrial fibrillation may even engender a form of cardiomyopathy, which usually shows complete recovery after adequate control of the arrhythmia. Unfortunately, the most feared complication of atrial fibrillation is not as reversible. Atrial fibrillation accounts for approximately 80,000 strokes per year in the United States [1]. The benefits of anticoagulation in this population are well known, but it has often been hoped that rigorous maintenance of sinus rhythm might obviate the need for this cumbersome treatment, forming a cornerstone for the argument in favor of rhythm control. As the Framingham data suggests, atrial fibrillation also confers a 1.5 to 1.9 fold higher risk of mortality independent of other cardiovascular diseases [2]. These incapacitating symptoms and serious complications underscore the importance of identifying the best approach to treating this frequently-encountered arrhythmia. The rhythm control strategy is appealing as it attempts to avert both the symptoms and the potential complications of the disease by maintaining sinus rhythm. However, this strategy can be complex in its execution as patients with persistent atrial fibrillation require a cardioversion to restore sinus rhythm. Success rates for electrical cardioversion vary from 79 to 94% depending on the amount of energy utilized and the manner in which it is delivered. Chemical cardioversion, although more simple to perform because no anesthesia is required, has less impressive success rates (with Class I agents being most effective) [3]. Regardless of how sinus rhythm is achieved, a rhythm control strategy may require multiple cardioversions, as atrial fibrillation will often recur. The maintenance of sinus rhythm between intervening cardioversions necessitates pharmacologic or nonpharmacologic treatments. Class I and III anti -arrhythmic agents have proven beneficial in this regard [4]. A meta-analysis demonstrated that quinidine resulted in twice as many patients remaining in sinus rhythm after one year. However, it also heralded the dangers of anti-arrhythmic therapy, as there was a three-fold increase in mortality in the quinidine group. Class I agents such as flecainide and propafenone were subsequently shown to have at least equal efficacy and better tolerability than quinidine [1]. Despite this, only approximately 50% of patients remain in sinus rhythm after one year. Some uncontrolled studies suggested that amiodarone might fare better in maintaining sinus rhythm, so this hypothesis was tested in the Canadian Trial of Atrial Fibrillation [5]. This study demonstrated a superior efficacy for amiodarone, with a 16-month follow-up showing that 65% of patients on amiodarone remained free of atrial fibrillation, compared to 37% of patients on sotalol and propafenone. Concern over potential adverse effects has always weighed against anti-arrhythmic drug use. In particular, the

2 specter of proarrhythmia looms over most Class I and III agents. Although possibly underestimated, Class IA agents such as procainamide, quinidine and disopyramide are reported to have an incidence of Torsade ranging from 1 to 3%. Sotalol, especially when administered at higher doses or in patients with concomitant diuretic use and renal dysfunction, can be proarrhythmic in 1 to 6% of patients [1,3]. For these reasons, the desire to maintain sinus rhythm has been tempered by the fear of inducing potentially life-threatening arrhythmias. The emergence of curative, non-pharmacological therapy for atrial fibrillation offers the potential for rhythm control strategies which obviate some of the adverse effects related to anti-arrhythmic medications. Haïssaguerre and colleagues demonstrated that AF was initiated by atrial extrasystoles originating, in the majority of cases (94% of triggers), in the pulmonary veins (PVs) [6]. The importance of this finding was that ablation of these ectopic triggers could result in a cure of AF. Initially, identifying ablation targets was an arduous task, especially when atrial ectopy was infrequent. In one study, as many as 32% of patients undergoing this procedure failed to have an ablation because there was insufficient ectopy to allow localization of the origin of the arrhythmia [7]. In addition, some patients can have multiple triggers, dramatically reducing the success rates for this intervention. Because of these obstacles, there was obvious interest in developing an anatomically-based procedure designed to electrically isolate these veins and prevent egress of triggering ectopics into the left atrium, thus preventing AF initiation. Newer mapping techniques involving the use of a circular catheter have allowed better identification of ostial exit points. Using such a catheter, PV isolation can be achieved by ablating the site of earliest activation within each vein. Pappone and colleagues showed that PV isolation could be performed using a three-dimensional electroanatomic mapping system. Circumferential lesions were made in the left atrium at a distance from the PVs. This technique provided a success rate of 80% at 10 months. Interestingly, recurrence rates were less in patients who had a larger ablation area [8], raising the possibility that elimination of PV triggers combined with reduction of atrial mass provided additional benefit. To date, these techniques remain somewhat difficult to perform, but as their utilization becomes widespread, they may prove to be interesting additions to the more common rhythm control methods. In contrast to rhythm control, rate control has frequently been viewed as a therapy of resignation, reserved only for patients in whom rhythm control had proved to be unfeasible. Nonetheless, this strategy has the advantage of providing symptom relief and preventing tachycardia-induced cardiomyopathy without necessitating anti-arrhythmic medications. However, in order for rate control to be effective, it must achieve certain target heart rates both at rest and during exercise. Current recommendations suggest that the goal of therapy should be ventricular rates of beats per minute at rest and during exercise [1]. These target heart rates are usually achieved with medical therapy. Beta-blockers, calcium channel blockers and digoxin, either alone or in combination have proved effective in achieving rate control. Utilization of betablockers and digoxin is preferable in patients with heart failure, whereas calcium antagonists are more appropriate for patients with pulmonary disease. Digoxin, however, provides less adequate rate control during exercise. The doses of these medications need to be titrated to achieve the target response. In certain cases, appropriate rate control cannot be achieved using only pharmacologic therapy, and in these instances, ablation of the atrioventricular (AV) node with pacemaker implantation should be considered. In this manner, both rapid rates and abrupt changes in rhythm are avoided. Initially, Scheinman et al described ablation of the atrioventricular junction with DC shocks for patients with refractory supraventricular tachycardias. Refinement of this technique in subsequent years involved the development of catheters capable of delivering radiofrequency energy instead of DC shocks in order to perform the ablation. This method proved to be more efficacious than DC catheter ablation, with success rates as high as 97% for achieving complete AV block, and this new form of energy delivery did not produce the same type of barotrauma observed with both high and low DC shocks, explaining the trend towards less significant ablation complications such as early sudden death, ventricular arrhythmias or cardiac tamponade. Current techniques have rendered the procedure successful in upwards of 98% of cases, with a low (1%) incidence of minor complications [4]. Despite current advances in catheter-based therapies for AF, AV nodal ablation and pacing remains a viable option for patients with drug-refractory AF for a number of reasons. Studies have shown that patients undergoing this procedure experienced a significant improvement in both quality of life indices and ease of activities of daily living. Fitzpatrick et al suggested that this improvement was more than subjective, as a significant reduction in doctor visits, hospital admissions and antiarrhythmic drug trials was documented in their 107 patients during the course of a 2 year follow -up [9]. The procedure may be particularly useful in preventing congestive heart failure caused by the rapid ventricular rates during uncontrolled AF, and in certain cases, an improvement in left ventricular function may be noted after the procedure. Furthermore, despite previous concerns about rendering patients pacemaker dependent and possibly augmenting the risk of

3 sudden death, recent studies confirmed that AV nodal ablation does not negatively impact on survival when compared to drug therapy [1]. Thus, both rhythm and rate control strategies carry with them multiple modalities and techniques with which to achieve the desired goal. Despite the potential adverse effects related to anti-arrhythmic therapy and the difficulties still encountered with curative ablation of atrial fibrillation, there exists a certain bias favoring rhythm control. There is an unquestionable allure in deploying efforts to achieve sinus rhythm, as many feel that this can alleviate symptoms, reduce the occurrence of heart failure, decrease the incidence of stroke and allow discontinuation of anticoagulants. Unfortunately, some of these assumptions are unfounded. It is important to bear in mind that certain studies suggesting an improved quality of life during rhythm control strategies were performed in patients with paroxysmal, not persistent atrial fibrillation. Paroxysmal atrial fibrillation, particularly when the patient alternates between sinus rhythm and atrial fibrillation very frequently, can be as incapacitating as structural heart disease. However, symptoms associated with persistent atrial fibrillation are more often related to rapid ventricular rates, and there exists good evidence, particularly in the atrioventricular nodal ablation data [9] that rate control can be quite effective at providing symptom relief, as this method, more. As detailed by Fitzpatrick and colleagues, ensuring adequate rate control resulted in significant improvement of the quality of life index and the ease of activities of daily living. Improvement of symptoms, then, may not necessarily hinge on whether a rate or rhythm control strategy is employed, but rather may be dependent on successful implementation of those strategies. Whereas rapid atrial fibrillation may precipitate acute congestive heart failure and cause ventricular dysfunction in the long term, both rhythm and rate control may be appropriate strategies for avoiding this complication. The merits of rhythm control are self-evident; but as previously stated, a well executed strategy of rate control can also confer reduction in emergency room visits, hospitalizations, and may reduce the progression to left ventricular dysfunction. Maintenance of sinus rhythm is occasionally touted as method of stroke prevention, however, it can be difficult to evaluate the effectiveness of a rhythm control strategy, as episodes of atrial fibrillation are frequently asymptomatic. The advent of holter monitoring, implantable event recorders, and rhythm data collection on pacemakers and defibrillators has also brought to light the importance of this phenomenom. Thus, it may be imprudent to discontinue anticoagulation in higher risk patients based simply on their lack of symptoms, especially since it is well established that the risk of stroke is equivalent in patients with paroxysmal and persistent atrial fibrillation [1]. Van Gelder and colleagues showed that patients treated with a rhythm control strategy had more frequent thromboembolic events that patients treated with rate control. Notably, of 21 patients with this complication, anticoagulant therapy had been stopped in 6 and 5 patients were in sinus rhythm at the time of the event [10]. The desire to cease anticoagulation is therefore not a compelling argument in favor of rhythm control. Recently, two major randomized control clinical trials compared the relative benefits of rhythm and rate control in the management of atrial fibrillation. The aforementioned Van Gelder study and the AFFIRM study [11] prospectively enrolled patients into each of the two treatment strategies. The European trial assigned 256 to rate control and 266 patients to rhythm control. The end point for this study was a composite of death from cardiac causes, heart failure, thromboembolic complications, bleeding, the need for a pacemaker, or serious adverse effects of the anti -arrhythmics. Twenty-two percent of patients in the rhythm control group reached the primary end point as compared to 17 percent in the rate control group, suggesting a trend favoring rate control. Of note, sinus rhythm was difficult to attain in this particular population, as 61% of patients in the rhythm control arm were in atrial fibrillation at the end of the study (90% in the rate control group). Thus, the majority of patients were subject to the risks of rhythm control while not necessarily achieving the possible benefits of sinus rhythm. The AFFIRM trial, though larger in scope, arrived at similar conclusions. The primary endpoint in this trial was overall mortality and was non-significantly higher in the rhythm control group (356 patients) than in the rate control group (310 patients). There was a much higher success for achieving sinus rhythm in this study, with its prevalence being 82.4%, 73.3% and 62.6% at 1, 3, and 5 years respectively. A total of 248 patients crossed over from rate to rhythm control, most often due to excessive symptoms of atrial fibrillation or heart failure. However, 594 patients crossed over from rhythm to rate control due to side effects of the medications or simple inability to maintain sinus rhythm. This study did not demonstrate any differences in quality of life indices between the two groups. It appears, then, that rate control is at least equivalent to rhythm control in terms of symptoms, serious complications, and mortality; although several important points were not addressed in these last two clinical trials. Both studies included only patients with previous episodes of atrial fibrillation, leaving open to debate whether a more conservative approach of rate control is appropriate in patients with a first episode of atrial

4 fibrillation who may have less propensity for recurrence. It also remains unclear whether non-pharmacologic methods of rhythm control such as pulmonary vein isolation may be of more benefit than the standard pharmacologic approach that was compared to rate control in these trials. Finally, one specific subset of patients, underrepresented in AFFIRM, are often felt by clinicians to require the additional contribution to cardiac output afforded by the atrial kick: those with congestive heart failure. The question of rate versus rhythm strategy in patients with heart failure is currently being addressed in a large multi -center trial [12]. Thus, while current data does not necessarily suggest we eschew any attempts at rhythm control for patients with persistent atrial fibrillation, it does exhort us to be more judicious in applying this strategy, particularly when recurrences are frequent and efforts at maintaining sinus rhythm appear ineffective. References 1. Fuster V, Ryden LE, Asinger RW, Cannom DS, Crijns HJ, Frye RL, Halperin JL, Kay GN, Klein WW, Levy S, McNamara RL, Prystowsky EN, Wann LS, Wyse DG, Gibbons RJ, Antman EM, Alpert JS, Faxon DP, Gregoratos G, Hiratzka LF, Jacobs AK, Russell RO, Smith SC, Jr., Alonso-Garcia A, Blomstrom-Lundqvist C, de Backer G, Flather M, Hradec J, Oto A, Parkhomenko A, Silber S, Torbicki A. ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the North American Society of Pacing and Electrophysiology. Circulation. 2001;104: Benjamin EJ, Wolf PA, D'Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation. 1998;98: Guerra PG, Talajic M, Roy D, Dubuc M, Thibault B, Nattel S. Is there a future for antiarrhythmic drug therapy? Drugs. 1998;56: Guerra PG, Lesh MD. The role of nonpharmacologic therapies for the treatment of atrial fibrillation. J Cardiovasc Electrophysiol. 1999;10:450-60; quiz Roy D, Talajic M, Dorian P, Connolly S, Eisenberg MJ, Green M, Kus T, Lambert J, Dubuc M, Gagne P, Nattel S, Thibault B. Amiodarone to prevent recurrence of atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators. N Engl J Med. 2000;342: Haissaguerre M, Jais P, Shah DC, Takahashi A, Hocini M, Quiniou G, Garrigue S, Le Mouroux A, Le Metayer P, Clementy J. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med. 1998;339: Gerstenfeld EP, Guerra P, Sparks PB, Hattori K, Lesh MD. Clinical outcome after radiofrequency catheter ablation of focal atrial fibrillation triggers. J Cardiovasc Electrophysiol. 2001;12: Pappone C, Oreto G, Rosanio S, Vicedomini G, Tocchi M, Gugliotta F, Salvati A, Dicandia C, Calabro MP, Mazzone P, Ficarra E, Di Gioia C, Gulletta S, Nardi S, Santinelli V, Benussi S, Alfieri O. Atrial electroanatomic remodeling after circumferential radiofrequency pulmonary vein ablation: efficacy of an anatomic approach in a large cohort of patients with atrial fibrillation. Circulation. 2001;104: Fitzpatrick AP, Kourouyan HD, Siu A, Lee RJ, Lesh MD, Epstein LM, Griffin JC, Scheinman MM. Quality of life and outcomes after radiofrequency His-bundle catheter ablation and permanent pacemaker implantation: impact of treatment in paroxysmal and established atrial fibrillation. Am Heart J. 1996;131: Van Gelder IC, Hagens VE, Bosker HA, Kingma JH, Kamp O, Kingma T, Said SA, Darmanata JI, Timmermans AJ, Tijssen JG, Crijns HJ. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med. 2002;347: Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, Kellen JC, Greene HL, Mickel MC, Dalquist JE, Corley SD. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002;347: Rationale and design of a study assessing treatment strategies of atrial fibrillation in patients with heart failure: the Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial. Am Heart J. 2002;144: Your questions, contributions and commentaries will be answered by the lecturer or experts on the subject in the Arrhythmias list. Please fill in the form and press the "Send" button. Question, contribution or commentary: Name and Surname:: Country:: Argentina Send Erase

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